Bocchetta A, Piccardi M P, Palmas M A, Chillotti C, Oi A, Del Zompo M
Center of Clinical Psychopharmacology, Department of Neurosciences "B.B. Brodie," University of Cagliari, Cagliari, Italy.
Am J Med Genet. 1999 Oct 15;88(5):522-6.
Association analysis of candidate genes may represent a strategy for clarifying the genetic components involved in bipolar disorder. Polymorphism at dopamine receptor genes DRD2, DRD4, and dopamine and serotonin transporter genes (DAT, SERT) has been used in previous association studies. Some authors have reported positive association between certain alleles and bipolar disorder, using the case-control design. In this family-based association study of DRD2, DRD4, DAT, and SERT, the distribution of parental nontransmitted alleles was compared with that of alleles transmitted to 53 Sardinian probands suffering from bipolar disorder. The transmission disequilibrium test (TDT) was used to detect any disproportionate transmission of alleles by heterozygous parents to affected children. No differences were found between the allele distribution of polymorphisms at DRD2, DRD4, DAT, and SERT in probands and parental nontransmitted chromosomes. TDT did not reveal any difference between transmitted and nontransmitted alleles. Our results do not support the hypothesis of a role for DRD2, DRD4, DAT, or SERT in bipolar disorder. Previously reported positive associations between DRD2 or SERT and bipolar disorder were conceivably due to stratification dependent on the case-control design, even though our sample might have failed to detect small associations due to limited power.
候选基因的关联分析可能是一种阐明双相情感障碍遗传成分的策略。多巴胺受体基因DRD2、DRD4以及多巴胺和5-羟色胺转运体基因（DAT、SERT）的多态性已被用于以往的关联研究中。一些作者采用病例对照设计，报告了某些等位基因与双相情感障碍之间的正相关。在这项关于DRD2、DRD4、DAT和SERT的基于家系的关联研究中，将父母未传递的等位基因分布与传递给53名患有双相情感障碍的撒丁岛先证者的等位基因分布进行了比较。采用传递不平衡检验（TDT）来检测杂合子父母向患病子女传递等位基因时是否存在不均衡传递。在先证者以及父母未传递的染色体中，未发现DRD2、DRD4、DAT和SERT多态性的等位基因分布存在差异。TDT未揭示传递和未传递等位基因之间存在任何差异。我们的结果不支持DRD2、DRD4、DAT或SERT在双相情感障碍中起作用的假设。尽管我们的样本可能因检验效能有限而未能检测到小的关联，但先前报道的DRD2或SERT与双相情感障碍之间的正相关可能是由于病例对照设计依赖分层所致。
